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HIV mRNA Vaccines-Progress and Future Paths (nih.gov)
204 points by mmastrac on May 25, 2021 | hide | past | favorite | 138 comments



The full text is available here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915550/

It's always good to remember just how crazy complicated and unusual HIV is, with its self-rewrite immune escape functionality.

The mRNA vaccine for covid-19 was very lucky, not only because coronaviruses are not the devilishly clever co-evolving with the host's immune system HIV type of things, but also because the spike protein was already "solved" ahead of the pandemic. By that i mean we knew how to create a version of the spike protein that doesn't require the full envelope to fold properly. The mRNA sequence was ready in January 2020, the rest was just manufacturing, testing and distribution.

The HIV vaccine will be most likely much more complicated, as the authors point out in the last chapter.

PS. Sometimes I wish I was a research doctor instead of a computer scientist, but I guess the grass is always greener :)


> Sometimes I wish I was a research doctor

The reality of being a researcher appears to be quite disappointing. Trapped between grant hunting and p-hacking the papers you need to churn out into high impact journals appears to be the grim reality.


I am (kind of) in research on the CS side, and I wish I was on the medical side.

The grant hunting, bullshitting, old-stuff-in-new-covers is all the same, but the problems and the topics are just so much more approachable, relevant, interesting, and the community seems to be "nicer".

But then of course, I know people that are in that area an were getting into research, and they did not paint a nice picture. And the community obviously can suck also once you're on the inside. And being a "researcher" without clinic duties is really not easy getting into in Europe it seems. Also, who wants to stop doing clinic completely, when this is what he trained for so long...

There are upsides and downsides to everything - I think it really depends on where your interests are.


I've done both. The crucial difference is that computer work is far more productive than bench work. If you spend a month at your computer, you will get something out of it. You can easily spend a month at the bench and come away with nothing at all.

Part of the secret to success in bench work is finding a seam which you can mine productively. You have some technique or system set up and working, and you can grind out findings from it. But it takes time to establish that seam, and it isn't necessarily anywhere near where the actually interesting problems are.

I worked on cell migration. We used a particular cell type that had very good, consistent migratory behaviour, which made it a good system. But it was a primary culture, made fresh from dissected tissue every day. Primary cultures are highly resistant to having DNA put into them. Pretty much all modern cell biology hinges on putting DNA into cells. I spent a year or so trying different techniques (including making adenoviral vectors!). Eventually, i found something which worked okay. But that was just the start of actually doing interesting work - the year up to that point had produced nothing. This is completely normal in bench work, but would be pretty shocking with computers.


I've done both too, but after a couple months at the bench, I always find myself spending most of my time trying to create robots to automate the work instead. Haven't gotten that to work out in the long run, so I just do programming now.


I guess at one point computing was more like that, in that to solve a new problem you may well have had to build yourself a new kind of computer or compiler first.


> the community seems to be "nicer"

Having worked as a programmer for molecular neurobiologists for two years: yeah, they are. Everyone's just hyped at how insanely fast things are developing. Everything I saw when I worked there felt cutting-edge. The engineering involved, the science produced, the speed at which new insights were being gained.

> And being a "researcher" without clinic duties is really not easy getting into in Europe it seems.

The trick is to go the molecular biology route instead, it seems


I'm a structural biologist and I can attest that we absolutely need more computer scientists in this field. The problems we are trying to solve are complex and there's so much room for improvement.

By the time someone is an expert on biology and then physics, there's not much mental capacity left for CS. And unfortunately people that start CS and move to biology are extremely rare.


What are the areas of research that need CS people and how would a grumpy CS/engineering MS/PhD make the switch? Um, asking for a friend!

As an undergraduate I actually first got into computing through a biology-computational project! My current work pays the bills, but my armchair dream switch to research - in biology or another science.


Chiming in as a former neuro-y person:

Really, it's the bare basics that they need a big hand with. In bio, a lot of the grad students have literally no calculus or math training outside of stats. They have no training whatsoever in CS, let alone programming. If they are programming, it's matlab, and then they use 15+ nested for-loops (true story). Hardcoded is the only way of things. Github is a way around gmail's 25mb limit. The PIs are these people with a few years under their belts and even worse habits. It's all hacked together with bubblegum and if-statements. And the time/money pressure is intense. They don't have the resources to start fresh with new habits or to learn three semesters of math.

I don't really know where to start on helping them, but it's pretty far back in the the chain. Honestly, given the constraints, it feels like they need someone to write programs for them in a pair coding style for free.


The reality of software engineering can be disappointing as well. Incompetent non-technical managers, business metric hacking before the funding round, and a ton of technical debt. But it pays much more.


Don't get me wrong. I hate software development just as much as academia. After 7 years in the industry, there is not a single shred of positive emotion towards software engineering left in me.


Wow, I'm incredibly sad for you. If I felt that way towards a field I've been working in since I was in the sixth grade and now for some 30 years of my life... well it wouldn't be pretty. Sounds like you're burned out. If software development is your passion, perhaps take a break and reconnect with yourself?


I mean, you're just talking about an academic research doctor. Which really only accounts for a small percentage of total researchers out there. I appreciate your trying to frame that his grass is actually quite green, don't just throw the baby out with the bathwater : )


Working in R&D in private companies can be not only well paid but very rewarding as well. A lot less struggle for resources if your idea pans out.


> ... because the spike protein was already "solved" ahead of the pandemic. ... The mRNA sequence was ready in January 2020, the rest was just manufacturing, testing and distribution.

Could I get some more context on this or a direction to start researching?

I feel this would be great information to share with the vax hesitate crowd. I have heard a few people say the vaccines are too new and not tested enough.


Off the top of my head, I believe it was due to research done during the SARS epidemic in the early 2000s that trailed off as funding dried up when it was no longer an immediate threat.


This is a good article on that specific sub-topic of the covid mRNA vaccines: https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behi...

Also, replying to the grandparent: vaccines per se are not necessarily safe out of the door, they're medical products and as such can have potentially many unforseen and troubling consequences. However, in the past all the unforseen consequences of any vaccine (whether still used, or since then retracted from the market due to problems) would become known a few months and a few tens of million people into the phase 3. That's when it is very, very safe to jump on board. And this is definitely already the case with all the popular covid vaccines.

To summarize: human data trumps everything in medicine, and we've had A LOT of data points.


> with its self-rewrite immune escape functionality.

Interesting! Could you elaborate on this or provide a link?

> but also because the spike protein was already "solved" ahead of the pandemic.

I would also be interested in further information on that?

Thanks


For the first you can just Google for "hiv rapid mutation", example: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414815/. The OP article contains a lot of details too.

For the second see something like "covid spike sequence modification", for example this seems like an accessible article: https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behi...

It was all thanks to the research on previous coronaviruses, MERS specifically. The Pfizer/Moderna vaccines have just copied it (of course that simple modification is not all it took, but that was definitely required for success).


With global HIV deaths in hundreds of thousands each year, but less evenly distributed and more stigmatized, will this vaccine be given emergency authorization as well, or is it likely to go through the full 10 year process?


Emergency Authorization is a regulatory matter, and thus isn't a global decision.

New Zealand did not use Emergency Authorization for the pandemic, because they had elimination so they were able to wait while their medicines agency performed full (but expedited) assessment for the Pfizer mRNA vaccine and gave a recommendation based on that assessment. As a result they didn't even begin vaccinating people until months after some other countries, but (because of elimination) they had zero deaths meanwhile.

So, in some countries regulators might decide an HIV vaccine is something that needs Emergency Authorization and in others not.

Another factor in what you're calling a "10 year process" is how long it takes to collect data from a Phase III trial. I think lots of people still do not appreciate why the Phase III trial for these coronavirus vaccines was so fast. The pandemic meant that huge numbers of people in your control group get infected. This is terrible news for them, some will die, but it means you get very rapid trial results.

So if you're confident that HIV has similar levels of spread, this is "good news" there too, the vaccine trials won't take very long to give results, regardless of whether you are intending to do Emergency Authorization or a normal process.


> So if you're confident that HIV has similar levels of spread

It does if you do phase III trials in the right countries. In South Africa, there's 15 million HIV cases give or take, and a million infections per year - so trials could yield results rather quickly...


Clinical trials are quite often global. I'd imagine any vaccine effort would be too.


In practice the trial will recruit participants from only a few countries. For example Pfizer's trial of BNT162b2 (their COVID-19 vaccine) recruited in the United States, Germany, Turkey, South Africa, Brazil and Argentina. But not for example Spain, Canada, Israel or Zimbabwe (picking countries off the top of my head at random).

In the ideal case you'd somehow randomly sample the world population, but practical considerations have to be taken into account. As a result it is often the case that we don't yet have a medicine targeted precisely at your gender, age, ethnicity, build, pregnancy status, co-morbidities, profession, and favourite musical genre, but ultimately the medicine which worked on another human who is quite unlike you in almost every way is surprisingly likely to be effective anyway, and so maybe you should try that meanwhile.


It may even be 100 years for all we know. It's not a problem of legislation. It's a problem of not knowing how to do this. This really has to be emphasised: it will most likely be much harder to achieve anything here. The covid vaccine was exceptional not only in the overall time-to-market but also in that it just worked on the first try. I'd wager a working HIV vaccine will instantly attract a Nobel prize, if not more than one.

Everyone has heard of the covid strains and the anxiety around them (are the strains much worse? will there be cross strain immunity?). This is like child's play compared to HIV, where essentially every infected person has a separate HIV variant, evolutionally crafted to evade the specific host immune system as best as it can. I would call it "amazing" had it not been inappropriate to call "amazing" a deadly disease.

Read the full paper, they go in detail on how the vaccine would have to create a "portfolio immunity" against the parts of the virus that are known to be most important. For example in terms of the humoral immunity they call them broadly neutralizing antibodies (bnAbs). Those will have to cover a range of variants.


Just to make things a bit more interesting (and grim): every HIV patient has multiple variants at the same time. In this regard HIV is pretty much like cancer :(

> Nucleotide sequences of the hypervariable V3 region of HIV-1 obtained from different organs of one patient demonstrated distinct viral variants.

https://pubmed.ncbi.nlm.nih.gov/8151287/


I think it's not just a question of the societal pressure. From the little I could understand in the paper, the HIV vaccine would be considerably more complicated than the Covid-19 ones, primarily do deal with all the immune escape issues. So it'd likely have a harder time getting authorized due the complexity of the mechanisms.


I am still waiting for silicon valley to 'disrupt' research. Places like

https://www.the-odin.com/

look scary at first blush. But if you've ever worked in a molecular biology lab, you know how competition, FOMO, and other pressures force shortcuts that should never be taken. In addition, the high traffic and 'density' of 'dangerous' agents and reagents makes errors exponentially more likely. These places are also high profile and as such targets for espionage as well as 'other' events (rhymes with error-ist and starts with a 't') .The resulting irony is that professional mol bio labs might be less safe for the workers and the environment than someone's basement. A contained low profile workplace is safer based on epidemiological arguments. An 'error' there is much more likely to result in a failed experiment than a disaster.



> I just hope we as humanity can develop cures quicker than we can breed viruses

Both HIV and COVID came from animal hosts originally. They weren't "bread" by humans.

> Watching covid varriants pop up worries me, but perhaps a quicker to production mRNA vaccine will allow us to remain ahead of it.

Well its possible that covid will mutate to escape the vaccine, its hardly a sure thing and hasn't happened yet (variants dont matter much if existing vaccines take care of them). Its entirely possible that new mRNA vaccines not only would be fast enough, but that we will never actually need them at all.


We detached this subthread from https://news.ycombinator.com/item?id=27271796.


> Both HIV and COVID came from animal hosts originally.

The jury is out on COVID. We don't know.


Even if it was a lab leak it was still probably of animal origin (the Wuhan lab collected and studied coronaviruses from bats).


We know with extremely high probability. It is genetically very close to bat coronaviruses. It is also not the first. Furthermore, a zoonotic coronavirus pandemic was already on the "Disease X" list, so it wasn't completely unexpected.

What we don't know yet is how it jumped from bats to humans. Is it direct? Is there an intermediate host? (pangolin?)

The more reasonable conspiracy theory is that the virus escaped from the Wuhan lab, possibly as a result of gain of function experiments. But originally, it is still bats, and what they could have done is not something nature is incapable of.


You're a conspiracy theorist and a retard


Would you mind not creating accounts to break HN's rules with like this? It only makes everything worse.

https://news.ycombinator.com/newsguidelines.html


Seeing how much widespread PrEP (daily pill to prevent getting HIV) usage has led to an increased amount of unsafe sex makes me worry about the next 'HIV'. Too many young people, specifically gay males, think as long as they are safe from HIV, they are safe enough. Unfortunately other STDs can have serious side effects, and in the long term can mutate into something more deadly.

That being said, progress towards an HIV vaccine will clearly lead to less deaths than an increased amount of unsafe sex, and remains a noble goal. I just hope we as humanity can develop cures quicker than we can breed viruses. Watching covid varriants pop up worries me, but perhaps a quicker to production mRNA vaccine will allow us to remain ahead of it.


We'll cure those too. Rather than worrying about that scenario, I'd rather consider what the world will be like when there are no STDs. It's certainly more amusing than fretting about something that has already happened(super-variants of run of the mill STDs).

As an aside, I wonder what role STDs played in the development of religion and the religious superstitions surrounding sex. Can monogamy survive in the long-term in a world without consequences to promiscuity?


I don't think historic STDs were a major component of the bans against promiscuity, since before syphilis was brought over from the Americas, you didn't really have life-threatening STDs around in the Middle East, Africa, Europe and Asia (HPV's link with cancer notwithstanding).

Much more likely, the problems with promiscuity were related to 'bastard' children and their role in inheritance; and to the father's uncertainty that a child was biologically theirs. In addition, many religious outlooks favor abstinence from bodily pleasures of all kind, so forbidding sexual pleasure and especially promiscuity seems well in tone with this.


Interesting that syphilis is theorized to come from the new world. I hadn't heard that before.

Did the old world have gonorrhea, herpes, genital warts, molluscum, trich, or any other visible STD? It seems like any one of those would be sufficient to cause a superstitious, iron age people to suspect something was plaguing the sexually promiscuous.


The old world had a lot of STDs, but nothing as destructive as syphilis.

Notably, when syphilis was introduced into the Old World population, it was described as a very severe acute disease. It only became more chronic after a period of adaptation that took several decades. This might have made the initial societal reaction more extreme.

https://www.everydayhealth.com/syphilis/painful-history-odd-...


> I don't think historic STDs were a major component of the bans against promiscuity, since before syphilis was brought over from the Americas, you didn't really have life-threatening STDs around in the Middle East, Africa, Europe and Asia (HPV's link with cancer notwithstanding).

Chlamydia rarely has life threatening complications but gonorrhea and hepatitis can kill. And there aren’t any STDs that don’t often cause infertility. Religions favored not screwing around because you’re guaranteed to get an STD eventually if you do, and that will very likely lead to infertility or worse.


>>Can monogamy survive in the long-term in a world without consequences to promiscuity?

The problem is that not everybody likes to share their partner. The likely consequence of a partner sleeping with other people is separation or divorce.

Also, I'm pretty sure that STDs have virtually never stopped anybody from cheating on their spouse if they wanted to. So no, I don't think that a lack of STDs will have much effect on monogamy, if at all.


Plenty of couples engage in consensual sex with other people… not always the result is doom and gloom.


Things get a bit more complicated once you get kids.


Only in availability, not in willingness. Besides, they will grow up.


They said 'not everybody', which is not an absolute construction.


>Can monogamy survive in the long-term in a world without consequences to promiscuity?

I guess define consequences? I sure as heck wouldn’t be ok with my wife having sex with other people just because STDs aren’t a problem… the consequence would be divorce with or without the STD.


> Can monogamy survive in the long-term in a world without consequences to promiscuity?

Well yeah, sex is cool and all but I don't like strangers or sharing.

I've never understood the "promiscuous" lifestyle that a different part of society seems to be natural at. Thankfully that's not the norm, just one of many subcultures.


What do you mean by can monogamy survive? Do you mean that in a world without STDs it would be abnormal for someone to expect an intimate relationship to be exclusive?


The intimate relationship is one component of monogamy, there's also having a steady nearly guaranteed sexual partner with low risks.

Ideally you're both monogamous so unless one had STIs before entering the relationship, it's incredibly unlikely either would acquire one and almost certainly not from intercourse but through some other means.

There are people more interested in the low risk stable sexual benefits of a trustworthy monogamous relationship. I personally doubt it's more than the number of people wanting an intimate relationship beyond sex though.


To add, relationships are not only about sex or a sexual partner. The emphasis in a proper relationship is on the partner part, not the sex part.


The intimate relationship is one component of monogamy

It's certainly not exclusive to monogamy.


> Can monogamy survive in the long-term in a world without consequences to promiscuity?

Consequences to promiscuity are not limited to STDs. Bad framing of the issue.


There are very little consequences to promiscuity today as long as you're not gay. Heterosexual vaginal sex is very low risk, especially with birth control being widely available. There's a bit of a gender disconnect in risk, but for a male it's even lower risk in terms of catching something than for the female.


Treatment resistant variants of syphillis and gonherea are on the upswing. Herpes is still a persistent problem. And these risks don't care whether you're gay or straight. I don't care what people do (inside the bounds of informed consent), but no matter what, wear a condom and don't share needles.

Otherwise, have a blast.


Is monogamy in humans the result of evolutionary pressures or a social construct to serve other purposes? With the right social indoctrination the majority might not care at all about monogamy, even find it strange and undesirable, ala Brave New World.


I think I care about the well-being of my family more than a cheap thrill.... by many orders of magnitude.


What if you don't have a family? In Brave New World there are no families. Technology plus social indoctrination have eliminated the need and desire for them.


A partner, of both the sexual and emotional variety, is far more satisfying than any random sexual hookup. Its the bedrock foundation of my life. Some sort of short lived satisfaction from hooking up with a random doesn't hold a candle to what we have. I'm not religious, we don't have kids, and we've been together for almost 20 years.


That's a hard pass from me. I rather we didn't use Brave New World and 1984 as guides on how to build the future.


Same for me. But of course that is because we have been conditioned to feel that way, isn't it?


It's more nature than nurture. Babies died in a Romanian orphanage because they were only fed and diaper changed and not held for example. I can't find the source right now but I did find this https://www.livescience.com/21778-early-neglect-alters-kids-...


Sure, but that's not something people feel comfortable hearing, judging by your downvotes.


It's just not true. We're not robots.


You know monogamy and pair-bonding are observed in many species? Several species of apes, monkeys, birds and fish have been observed to implement life-long pair bonding.

From a cold, logical perspective there are certainly evolutionary benefits to having a pair-bond not least of which is future certainty of care, for yourself and your joint offspring.


From a cold logical perspective, it would be advantagous to have many mates you share with others, that all take care of any offspring, since then even in the event of the death of the biological parents, the social parents can continue care for the offspring. Redundancies and failsafes are better if you have more.


Even for pair-bonded species, DNA testing has repeatedly found offspring to have fathers different from the mate.

So maybe natures optimal path is closer to pair-bonding + promiscuity, rather than either on their own?


You know many of us can’t find a partner anyway, right? “Unchecked promiscuity” isn’t really a problem.


We also now have paternity tests readily available, so we dont neccesarily need marriage for inheritence purposes.


There are understated psychological consequences to casual sex, particularly for females. Only in my 30s did I begin to understand the damage that my ostensibly harmless casual relations caused to many past partners, particularly those who grew attached before the end of the casual relationship.

Pair bonding is crucial to social organization and casual encounters erode the psychological capacity for such bonds, without nullifying the innate human desire for long term companionship. The result in a "sex positive" society is a growing proportion of perpetually lonely and frustrated people, or dysfunctional relationships. One of the few instances in my opinion where ignorance truly may be bliss.

So, to your question, it's quite possible that we will rediscover the purpose of monogamous marriage, if we can reason past the barriers of some recent ideologies.


> There are understated psychological consequences to casual sex, particularly for females. Only in my 30s did I begin to understand the damage that my ostensibly harmless casual relations caused to many past partners, particularly those who grew attached before the end of the casual relationship.

Do you have any reading material on this to suggest?


Marriage has often had little to do with monogamy. Adultery was the norm throughout the centuries, particularly when marriage was forced, had to happen very early in life, and when divorce was not an option. Prostitution was often utilized most by the married, not by bachelors.


Monogamy and casual sex are not opposites. You can both monogamously engage in casual sex, and be non-monogamous and reject casual sex.


We'll cure those too.

Sure, but after how many people get sick? Seems like a very dismissive comment.


I worry that you're worried about a group of people freely participating in activities that could lead to further mutations of viruses that could spread to people.

It's a bit of paranoia and maybe even unconscious bias against the group mentioned you're not aware of.

Heterosexual unsafe sex is just as likely to lead to virus mutations and it's certainly a higher proportion of the population, yet you choose to point out gay males in particular?


It's vastly less likely to transmit HIV to the penetrative partner, so the fact that it's possible for gay males to perform both roles makes it more likely to spread.

It's oversimplifying, but it's not wildly off base.


Right, but isn't this dicussion about _other_ viruses, not HIV (due to PrEP)?


The same could be said for the pill and heterosexuals, no?


People do make that argument, yeah. I’m not well versed in the subject of heterosexual or homosexual sexual statistics to opine on either, I just wanted to clarify what was being discussed :)


It's not paranoia since people who engage dangerous acts are also danger to society, just like drunk driving or the corona deniers. Just because the group were talking about is gay men doesn't mean the same doesn't apply. I've yet to met a gay men who disagrees and vast majority of them think it's problematic.


[flagged]


This appears to be a discussion about the dangers of rampant unsafe sex, not about prep. I know tons of straight men and women who have unsafe sex.


> Unfortunately other STDs can have serious side effects

You're not technically wrong. It's just that up until very recently the ones not preventable by vaccine (HPV, albeit stupidly expensive for men to get vaccinated for which of course means that men don't get vaccinated for it) were mostly immediately obvious and always easily solved by a single dose of antibiotics (basically everything except HIV, HPV, and herpes, which isn't life threatening).

Our impending antibiotic resistant apocalypse is of course terrifying.


>Our impending antibiotic resistant apocalypse is of course terrifying.

This is my main concern. We as a species seem to always be so sure we can engineer our way out of a catastrophe by focusing on reaction to problems vs prevention of problems and always pass costs to the future. I'm all for keeping reactive skills top notch but we need to think about simple and easy preventative measures.

The HPV vaccine reference is a great example. Men should also get vaccinated as a preventative measure but we play it off as too costly or low risk. Men partaking in anal sex can get HPV and not even know it, sometimes leading to penis or colon/anal cancer later in life. It's especially bad because men will likely go long periods of time completely unaware of such an infection. We vaccinate young girls because we know they're all at risk but we often don't vaccinate young men because we don't know who will or won't end up having anal sex and culturally assume men are somehow invulnerable to it because of it.


> Men partaking in anal sex can get HPV and not even know it

Men partaking in _any_ kind of sex can get HPV and not know it. It's just as transmissible through oral and vaginal sex, and vaccination among women is also extremely poor in the US.


>Men partaking in _any_ kind of sex can get HPV and not know it.

True, it's definitely possible to overlook or ignore, although symptoms of HPV are far more likely to be observed anywhere else than inside the anus or vagina.


I presume this is in the US? In the UK for example the HPV vaccine for gay men is free on the NHS. I'm sure the same is true for many other countries too.


If I remember rightly, the US does routinely vaccinate everyone against HPV as teenagers regardless of gender - it's the UK that historically only vaccinated girls. (Though this changed very recently, it obviously still leaves a bunch of men unvaccinated.) There's some kind of recent vaccination program for gay men, but that only started a couple of years ago and requires them to actively seek out vaccination.


As an anecdote, when I asked about getting it, I was told that it would not be covered by my insurance and would cost me $500. That price is out of reach for the vast majority of Americans.


How old are you? If you are over 26, I don't think they legally have to pay for it.


In the Netherlands, boys also get the HPV vaccine since this year. It's now part of our (free) National Immunisation Programme.


> albeit stupidly expensive for men

WHY??? 620€ in Germany/Austria for 3 shots is absolutely outrageous.

HPV is responsible for a high amount of penile, anal and mouth/throat cancers. Even if you already have or had a HPV infection, the vaccine can protect you from getting it again or strains you don't have yet. There is some evidence that the HPV vaccine can act as cure for existing infections. +anyone vaccinated protects unvaccinated people.


>anyone vaccinated protects unvaccinated people.

Fellow German here, this is what I really don't understand, this is the same argument that is used for every other vaccine. Why not this one?

Is it really 620€ I was thinking of getting it at some point, but that's a steep price.


You know why. US drug conglomerate Merck patented anything to do with the HPV vaccine and is charging as much as it can to maximise profits - netting twice the total R&D costs for Gardasil every year on it.


Humanity has had lots of very unsafe sex for the last one million years and survived just fine. The risks are more to the individual than the species as a whole.


Humanity also didn't have widespread intercontinental travel for most of the past 1 million years.

We all live in a single Petri dish now. A few thousand years ago humanity existed in many many isolated communities and was much more resilient to disease. Regular pandemics every ~10 years are very much a side effect of technology.


I don't think that's true. Look at the death count by various years https://en.wikipedia.org/wiki/List_of_epidemics . Better health care seems to more than offset the extra risk from air travel.


Not only air travel. Sea travel. A thousand years ago there was an entire backup continent (the new world). And plenty of isolated communities were decimated when explorers came and brought alien diseases. Air travel just accelerated the process so that pandemics can spread within days rather than years and the effects can be seen in real time.


Sure, I’m sure they enjoyed their life expectancy of under 30 years.


When life expectancy was 30 years, it was because many children didn't live past the first year; still, 70 year olds were common in hunter-gatherer societies.


Common doesn’t mean that most people made it. In a world where you can die for a cut, a hunter doesn’t last to be 70 very easily. This is one of those counter-myths that I’ve been seeing too often lately.

The comment about dying early made sense: Just because we lived with unprotected sex for the last million years (and we changed genetically due to some viruses that we got along the way) it doesn’t mean that we’re now still willing to bear the consequences.

I’m willing to bet that nowadays we have far more sexual partners than we’ve had since we started “society”


Seriously? The only person I know my age that’s getting laid is...married to his wife. Where is this moral panic coming from? If anything the new moral panic is young people aren’t having sex at all.


This is one of those counter-myths that I’ve been seeing too often lately.

As opposed to people being ignorant about statistics and constantly parroting crap like "people only lived to 30 before modern medicine"?


To your last point, it’s possibly not true if you track what is happening in Japan and now starting in the west.

Many people can go their entire lives having the internet as their sole partner.


I don’t think they’re a huge amount of people, at least currently. It looks like about 30% of Americans between 25 and 50 have never been married. That means at least 70% of that group has been married, more will marry in their lifetimes, and likely a large amount of people fornicate out of wedlock.

That indicates that the vast majority of people has at least one sexual partner, with many having a lot more thanks to sexual liberation.

For the record, I’m not saying that this is a bad thing at all. I was just alluding to the fact that we can’t compare life and expectations of safety to what it was even 100 years ago, let alone over “millions of years”


Irrelevant - none of the STDs that have survived to this day and that also existed in prehistoric times would have been a major cause of death, except perhaps as complications in child birth.


yep, and we got some stuff from the Neanderthals as well....


HIV didn't come about because of unsafe sex, it was a freak accident involving blood. And as far as I can tell, in the history of modern humans there have been three STDs that have been life-threatening: Siphilis, HPV and HIV. So I wouldn't worry too much.

Remeber that unsafe sex is the natural norm, especially if you don't have to worry about unwanted pregnancy (as in the case of gay people). Safe sex only truly became a necessity because of HIV, an extremely recent phenomenon.


First of all, the most dangerous word in the world is "safe"- there is no such thing. It's an illusion. You are not safe, you will get sick and die one day. We all will.

Also, people have been having "unsafe" sex for over 40,000 years. There's been gay unsafe sex and straight unsafe sex going on all that time.

I'm not sure how we all made it.


> I'm not sure how we all made it.

I am not a scientist or any kind of expert. But I thought I read somewhere that there are some ape species for whom SIV is endemic and harmless. Others get sick and die.

So maybe it just takes time for a species to adapt and it's very deadly right now because humans haven't been exposed for very long.


A lot of deadly diseases become deadly by crossing the species barrier. Long term its a better survival strategy to not kill your host.


"We" are subject to survivorship bias. Plenty of people did not make it and their bloodlines are long extinct.

The difference between Stone Age and today is that our civilization managed to conquer most really serious risks that used to shorten the lives of people under, say, 70. Famines, unsafe water, most bacterial diseases are well under control. So, of course, the roster of threats now changed, some of them being civilizational (road accidents), some of them being relatively small holdovers from the ancient days, such as STDs, plus the very aging that makes our mortality curves shoot up in the old age.

But yes, realistically, people are going to bareback one another all the time. Which means that vaccines and cures for whatever bug is transmitted like that are necessary.


People are going to have unsafe sex for the entirety of human existence, period. Even during the height of the HIV epidemic in the 80s they were still doing it. We should accept that truth and work now to be prepared for the next pandemic.

If you insist on people using condoms just in case a novel virus is circulating, then we should all be wearing masks too at all times well into the future. Respiratory viruses can be just as bad as sexually transmitted ones.


> makes me worry about the next 'HIV'. Too many young people, specifically gay males, think as long as they are safe from HIV, they are safe enough.

So, first off, you might have a valid point but your approach sounds pretty biased. The wild generalizations about behavior, especially stigmatized behavior from a marginalized group, detracts from point about concern over a super-virus. Yes, gay men are often the topic of convo when it comes to HIV but it's not like they're the only ones passing around STDs.

Also, I'm not sure its true that Prep has had a material increase in unsafe sex. Most gay men seem to think of it more as a means to not worry about dying from sex instead of an opportunity to dramatically change behavior. Thanks in-part to HIV gay men are probably also the population with the best insight into their sexual health - so if a concerning new STD did spread, they'd be the first to take the individual responsibility to stay regularly tested and informed.

Birth-control and abortion and other related tools likely had a similar affect on heterosexual sex that prep had on gay men. There is a lot more heterosexual people to pass things around too. So calling out gay men might not be the most important piece to your worry about promiscuity leading to a super-virus.

Prep-induced gay promiscuity inducing a new pandemic of super-STDs really sounds like a bad talking point for an extremist politician in a conservative country. Obviously, its possible, however improbable, but its probably not the best way to express this concern.


"Too many young people, specifically gay males" Do you have any data to support this allegation?


Not OP, and generally don't agree with their point, but this passes the general sanity test.

Considering PREP is targeted almost exclusively to gay men, and HIV is mostly a concern among the sexually active gay male population, saying "young, gay, men" is pretty fitting.

Obviously the value-judgement about how much sex is too much or too risky can't have data to back this up. To me, as long as there is a net reduction in risky behavior that might impact society (not spreading a disease faster than eradicating it), its probably good, but this doesn't seem to be OP's view.


I should have cited the whole sentence.

I do not want to discuss a higher incidence of HIV in the group of gay males compared to the whole population. That is a fact that is attributable to the fact that unprotected anal sex comes with a higher infection risk then unprotected vaginal sex.

But the OP claimes that "specifically [young] gay males think as long as they are safe from HIV, they are safe enough." That may be the result of unfortunate wording. But if not it is an allegation that the OP will have a very hard time to prove.


While I agree with you, the truth is that among gay men, the use of condoms was already in sharp decline despite HIV, and before PrEP being so ubiquitous years ago. So while this medicine might have made people forgo condoms faster, it also came at the right time to prevent youths from a life with HIV. Furthermore, each new PrEP prescription (prepscription?) requires tests for a series of common STIs so at least guys are getting tested regularly now.


There's no way around that issue, it all stems from education and awareness.


There's a wonderful book called No Magic Bullet by Allan M. Brandt that discusses how rates of syphilis and other STIs rose after there were effective treatments.

To your comment, I'd at least say there's evidence that treatments to previous STI epidemics hasn't caused the downfall of humanity, and so a vaccine or treatment for HIV/AIDS likely won't either.


Does the book account for the effect of more people undergoing testing once there was an effective treatment? If there's no effective treatment, testing mostly benefits others.


Treatments and vaccines are different, though.


In specific, you can get syphilis again after being treated for it, while a vaccine normally confers permanent immunity.


this is interesting, so you're saying producing something like a "super STD" much like how antibiotic resistant strains of bacteria, ie superbugs, are bred in hospitals for example. So in this petridish of unprotected sex we create the conditions for the formation super STDs?


I don't think it works that way. Why would unprotected sex lead to super-std's? People getting a cold on a regular basis dont generally lead to super-colds.

You of course may get drug resistence in std's just like other non-sexual infections, but im not sure why the emphasis on unprotected sex.


it's a good question, I always thought STDs were more infectious just because their direct route of transmission into the body with the large mucous bodies that are involved. Thinking about that recent term that's come up in COVID with viral load, it seems like with an STD you're opening the doors to a direct viral/bacterial load punch unlike the diffuse air transmission routes that drop like a mold spore and have to reproduce. I'm curious now when it comes to STDs is there any way to quantify just how much concentration/load shows up in body fluids and how potent the infectiousness would be for those fluids given that concentration.

But now that I think about it, I'm curious which cavities in the body present the widest mucosal surface areas if you cut and open them up and measure them. The pharynx, the throat, the anus and colons, the urethra, the vagina cervix and uterus, how do each of those measure out. I've heard the colon is susceptible to infection because of the large network of lymphatic tissue just on the otherside and because it's designed to absorb stuff being the last mile of the digestive tract where traces of anything left behind at that final stage and still useful can be absorbed by the body. The application of suppositories come to mind in this space.

Another angle might connect with the point brought up by the other individual about bacteria being a frequent origin of STDs, and bacteria generally share genetic material from what I understand. Maybe that bacteria to bacteria mingling is where the risk comes in?


> I'm curious now when it comes to STDs is there any way to quantify just how much concentration/load shows up in body fluids and how potent the infectiousness would be for those fluids given that concentration.

Yes, this data exists and can be measured. Viral Load, detectable load, etc are common terms when discussing HIV.

Not a doctor, but from what I've heard the colon is the mucus membrane that presents the greatest risk for STD transmission.

> Maybe that bacteria to bacteria mingling is where the risk comes in?

I think its "simpler" in that we've seen bacteria become resistant to antibiotics. So bacterial infections could become resistant. I'm not sure its a valid concern since most people will kill the infection before spreading it (which increases rate of mutation), which is easier to do for an STD than something airborne by a hospital patient who can't leave.


> Maybe that bacteria to bacteria mingling is where the risk comes in?

Generally bacteria-based stds are not the scary ones as we have very good treatments for them (antibiotics).

Antibiotic resistence is a concern of course, but still, virus based stds are much scarier.


> im not sure why the emphasis on unprotected sex

Probably just because the thread context is a rise in unprotected sex and a coincident rise in STI transmission.


> People getting a cold on a regular basis dont generally lead to super-colds.

This is actually a good point applicable to the broader context, that I hadn't really thought about. Billions of people get cold/influenza infections every year. Why don't we see more mutations of strains that are highly virulent/tending to more severe outcomes?


To be fair, influenza is a bit of a different beast than colds, it mutates a lot relative to other diseases. We do get bad strains of influenza from time to time. Most famously in 1918, but we had a flu pandemic as recently as 2009.


Influenza can cross species boundaries and that's what tends to make it generally more dangerous than the natural mutations in seasonal flu. The "swine flu" pandemic of 2009 involved bird and pig influenza viruses mixing genetic materials with human influenza.


Because there is no evolutionary pressure on viruses towards more severe outcomes - if anything, the opposite is true. Higher virulence is occasionally seen though, as was the case with the swine flu some years ago.


> Because there is no evolutionary pressure on viruses towards more severe outcomes - if anything, the opposite is true.

I get this, but it doesn't intuitively follow to me that the incidence of severe strains would be as low as they are. The evolutionary pressure against severe strains shouldn't be enough to stop them from emerging in the short term. And yet, for example, all the severe coronavirus strains seem to be zoonotic, rather than mutations of strains already circulating in humans.

> Higher virulence is occasionally seen though, as was the case with the swine flu some years ago.

I guess higher virulence is also hard to measure. If there's a rhinovirus strain one year that infects twice as many people as normal, who's going to notice that?


I imagine that with normal virus evolution, many people already have at least partial immunity to the new strain as its a minor change, where if it crosses the species barrier that's a bigger "jump" so probably nobody has partial immunity so its more unchecked.

(Just pure speculation. Not my field)


COVID-19 is unique in the sense that it sits in a neat "uncanny valley" of virulence and lethality where it's able to attack our healthcare infrastructure (aided by modern travel), but is sufficiently non-lethal that it can keep spreading. The notable issue with SARS (which was incredibly lethal) was that the incubation time was too short - one or two days before you weren't going anywhere, way too high visibility.


Drug resistant STIs are not just hypothetical anymore. https://www.who.int/news-room/fact-sheets/detail/multi-drug-...

I guess maybe it's not widely known, but half of STIs are bacterial, so antibiotic resistance is exactly the thing people are worried about.




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